General Method for Ni-Catalyzed C-N Cross-Couplings of (Hetero)Aryl Chlorides with Anilines and Aliphatic Amines under Homogeneous Conditions Using a Dual-Base Strategy

A general method for the Ni-catalyzed Buchwald-Hartwig amination of (hetero)aryl chlorides using both anilines and aliphatic amines under homogeneous conditions has been developed. Key to the success of this method is the implementation of a dual-base strategy that utilizes an amine base combined with a soluble halide scavenger that allows for the use of a single air-stable, commercially available Ni(II)-precatalyst and phosphine ligand [(R,S)-Josiphos] combination to promote aminations across a broad scope of (hetero)aryl chlorides and pharmaceutically relevant amine nucleophiles at catalyst loadings as low as 1.0 mol %.